POS0529 LONG-TERM LOCAL JOINT DAMAGE PROGRESSION IN RHEUMATOID ARTHRITIS IS RELATED TO CUMULATIVE LOCAL CLINICAL JOINT INFLAMMATION
Authors: S. Heckert, S. A. Bergstra, Y. Goekoop-Ruiterman, M. Güler-Yüksel, W. Lems, M. Van Oosterhout, T. Huizinga, C. Allaart
Journal: Annals of the Rheumatic Diseases (2022)

Background Previously we showed that joint inflammation in rheumatoid arthritis (RA) tends to recur in the same joint, suggesting local factors contributing to joint inflammation. In the same study population, we now investigated whether cumulative local joint inflammation is associated with local radiographic damage progression. Objectives To investigate whether there is an association between long-term cumulative joint swelling and progression of radiographic damage in treated-to-target patients with RA. Methods Data from the BeSt study were used, in which newly diagnosed patients with RA (ACR 1987 criteria) were treated-to-target (DAS ≤2.4) during 10 years. Local joint swelling (yes/no) was determined by clinical evaluation by trained nurses of all hand and foot joints at 3-monthly study visits. Yearly radiographs of hand and feet were scored for radiographic joint damage (Sharp-van der Heijde method) in random order by two independent readers who were blind for clinical results. Per joint, damage was expressed as the percentage of the maximum possible damage score, to account for differences in maximal scores per joint. Missing values were imputed using the last observation carried forward method. A generalized linear mixed model was used to assess the association between local joint swelling over time (i.e., percentage of study visits with observed local joint swelling) and degree of joint damage at the end of follow-up. Joints were clustered within patients. The model was adjusted for baseline damage and follow-up duration. To test the association between cumulative local joint swelling and joint damage as a local or a general inflammation effect, we did two analyses. First, we additionally adjusted the primary analysis for the mean disease activity score (DAS) over time. Second, we did a permutation test to study whether joint damage progression was better predicted by joint swelling in the joint itself than by joint swelling in randomly selected other joints, which is indicated by a p-value of &lt;0.05. Results Of the 16,150 joints of 475 patients with at least one year follow-up with both radiographic and joint swelling assessment available, 16% (2,564) had radiographic joint damage (damage score ≥ 0.5) at the end of follow-up. Median (IQR) follow-up time was 10 (6-10) years. Of the joints with damage at the end of follow-up, 46% (1,163) was swollen at baseline, versus 36% (4,818) of the joints without damage. The median (IQR) percentage of visits at which joint swelling was observed was 6 (0-17) and 3 (0-8) for joints with and without joint damage respectively. We found a β of 0.13 (95% CI 0.12 to 0.14) for the association between cumulative local joint swelling and local progression, that is, with each 1% increase in the number of visits with local joint swelling, local radiographic joint damage progression on average increased with 0.13 percent. In an analysis with 10-years completers only (both baseline and year 10 damage score available, n = 9,520) we also found an association between cumulative local joint swelling and local radiographic damage (β 0.24, 95% CI 0.22 to 0.26). The association was also found in a subset of joints that were swollen at least once (β 0.20, 95% CI 0.18 to 0.22), indicating that joint damage is not only associated with ever-occurrence but also with the frequency of joint swelling. This association was found for both erosions (β 0.07, 95% CI 0.07 to 0.08) and joint space narrowing (β 0.21, 95% CI 0.19 to 0.22). The results of the primary analysis did not change after adjustment for DAS over time. The permutation test showed that local joint damage progression was better predicted by the frequency of joint swelling of that joint, than by joint swelling frequency of other joints (p&lt;0.001). These results indicate a local, rather than a general, inflammation effect. Conclusion Cumulative local joint swelling over time is associated with joint damage progression in the same joint in treated-to-target (DAS ≤2.4) patients with RA. Our results indicate that this is a local effect rather than an effect of general disease activity. Disclosure of Interests Sascha Heckert: None declared, Sytske Anne Bergstra: None declared, Yvonne Goekoop-Ruiterman: None declared, Melek Güler-Yüksel: None declared, WIllem Lems: None declared, M. van Oosterhout: None declared, Thomas Huizinga: None declared, Cornelia Allaart Grant/research support from: The original BeSt study was funded by a research grant from the Dutch College of Health Insurances with additional funding from Schering-Plough BV and Centocor Inc.